Bioluminescent imaging of intracranial vestibular schwannoma xenografts in NOD/SCID mice.
OBJECTIVE
Intracranial vestibular schwannoma xenografts can be successfully established and followed with bioluminescent imaging (BLI).


BACKGROUND
Transgenic and xenograft mouse models of vestibular schwannomas have been previously reported in the literature. However, none of these models replicate the intracranial location of these tumors to reflect the human disease. Additionally, traditional imaging methods (magnetic resonance imaging, computed tomography) for following tumor engraftment and growth are expensive and time consuming. BLI has been successfully used to longitudinally follow tumor treatment responses in a noninvasive manner. BLI's lower cost and labor demands make this a more feasible approach for tumor monitoring in studies involving large numbers of mice.


METHODS
Patient excised vestibular schwannomas were cultured and transduced with firefly luciferase expressing lentivirus. One million cells were stereotactically injected into the right caudate nucleus of 21 nonobese diabetic/severe combined immunodeficient mice. Schwannoma engraftment and growth was prospectively followed for 30 weeks after injection with BLI. After animal sacrifice, the presence of human tumor cells was confirmed with fluorescent in situ hybridization.


RESULTS
Eight (38%) of 21 mice successfully engrafted the schwannoma cells. All of these mice were generated from 4 (67%) of the 6 patient excised tumors. These 8 mice could be differentiated from the nonengrafted mice at 21 weeks. The engrafted group emitted BLI of greater than 100,000 photons/s (range, 142,478-3,106,300 photons/s; average, 618,740 photons/s), whereas the nonengrafted group were all under 100,000 photons/s (range, 0-76,010 photons/s; average, 10,737 photons/s) (p < 0.001). Fluorescent in situ hybridization analysis confirmed the presence of viable human schwannoma cells in much greater numbers in those mice with stable or growing tumors compared with those whose tumors regressed.


CONCLUSIONS
We have successfully established an intracranial schwannoma xenograft model that can be followed with noninvasive BLI. We hope to use this model for in vivo testing of schwannoma tumor therapies.
Neff
Brian A
BA
Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic School of Medicine, Rochester, Minnesota 55905, USA. neff.brian@mayo.edu
Voss
Stephen G
SG
Allen
Cory
C
Schroeder
Mark A
MA
Driscoll
Colin L W
CL
Link
Michael J
MJ
Galanis
Evanthia
E
Sarkaria
Jann N
JN
D000818:Animals; D001921:Brain / Q000473:pathology / Q000601:surgery; D005260:Female; D016515:Genes, Neurofibromatosis 2; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016086:Lentivirus / Q000302:isolation & purification; D008163:Luminescent Measurements / Q000379:methods; D008279:Magnetic Resonance Imaging; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009464:Neuroma, Acoustic / Q000473:pathology / Q000601:surgery* / Q000821:virology; D014183:Transplantation, Heterologous